The Center for the Neurobiology of Addiction Treatment (CNAT) is a new version of a PSO Center at Wake Forest University Health Sciences that has been continuously funded by NIDA since 1991. The Specific Aims are: 1. to provide a novel mechanism of interaction between NIDA Investigators at Wake Forest University to examine neurobiological mechanisms of cocaine pharmacotherapies, using tightly interacting projects to ensure an effective collaborative structure; 2. to provide a formal structure of collaborative interactions between our Center and our clinical partners at two NIDA-funded clinical centers, thus providing a novel translational component to our research; 3. to provide a focus for the training of students and postdoctoral fellows in contemporary methods for investigating the neurobiological basis of drug abuse; 4. to serve as an information source to both the lay and scientific community on issues related to the neurobiological aspects of drug abuse. The scientific theme of the Center is focused on examining the neurobiological mechanisms of action of drugs that are currently used, or proposed for use in the clinic for treatment of cocaine addiction; these studies will begin with topiramate, and proceed with other potential treatment agents including modafinil, D3 dopamine antagonists, orexin antagonists, and others. The Center will accomplish these goals through the activities of two cores and three major projects. The projects are designed to be highly interactive, with each project's activities dependent on results obtained from the other two projects. Project 1 will examine effects of drug treatment on various behavioral models in both rats and monkeys; Project 2 will explore how these drug treatment paradigms affect functional consequences in brain through neuro-imaging and voltammetry; and Project 3 will explore how these drug treatments affect gene and protein expression, receptor function and signal transduction systems in brain tissue obtained from the other Projects. A unique aspect of the Center is the close interaction with two clinical Centers (at the University of Pennsylvania and the University of Virginia) to provide translational capabilities. The Administrative Core will coordinate Center activities, conduct a pilot studies program, and provide for annual meetings with clinical Centers. The Tissue Core will provide uniform sets of brain tissue samples to the projects for individual studies. These projects utilize several animal models and technologies uniquely developed by the Center investigators over the previous years of its funding history.